title: GABAergic excitation of vasopressin neurons: possible mechanism underlying sodium-dependent hypertension.
abstract: BACKGROUND
  Increased arginine-vasopressin (AVP) secretion is a key physiological response to hyperosmotic stress and may be part of the mechanism by which high-salt diets induce or exacerbate hypertension.
  
  
  OBJECTIVE
  Using deoxycorticosterone acetate-salt hypertension model rats, we sought to test the hypothesis that changes in GABA(A) receptor-mediated inhibition in AVP-secreting magnocellular neurons contribute to the generation of Na(+)-dependent hypertension.
  
  
  RESULTS
  In vitro gramicidin-perforated recordings in the paraventricular and supraoptic nuclei revealed that the GABAergic inhibition in AVP-secreting neurons was converted into excitation in this model, because of the depolarization of GABA equilibrium potential. Meanwhile, in vivo extracellular recordings in the supraoptic nuclei showed that the GABAergic baroreflexive inhibition of magnocellular neurons was transformed to excitation, so that baroreceptor activation may increase AVP release. The depolarizing GABA equilibrium potential shift in AVP-secreting neurons occurred progressively over weeks of deoxycorticosterone acetate-salt treatment along with gradual increases in plasma AVP and blood pressure. Furthermore, the shift was associated with changes in chloride transporter expression and partially reversed by bumetanide (Na(+)-K(+)-2Cl(-) cotransporter inhibitor). Intracerebroventricular bumetanide administration during deoxycorticosterone acetate-salt treatment hindered the development of hypertension and rise in plasma AVP level. Muscimol (GABA(A) agonist) microinjection into the supraoptic nuclei in hypertensive rats increased blood pressure, which was prevented by previous intravenous V1a AVP antagonist injection.
  
  
  CONCLUSIONS
  We conclude that the inhibitory-to-excitatory switch of GABAA receptor-mediated transmission in AVP neurons contributes to the generation of Na(+)-dependent hypertension by increasing AVP release. We speculate that normalizing the GABA equilibrium potential may have some utility in treating Na(+)-dependent hypertension.
authors.affiliation: From the Department of Physiology (Y.-B.K., Y.S.K., W.B.K., F.-Y.S., S.W.L., H.J.C., H.C.H., Y.I.K.), and Neuroscience Research Institute (Y.-B.K., Y.S.K., W.B.K., F.-Y.S., S.W.L., H.J.C., H.C.H., Y.I.K.), Korea University College of Medicine, Seoul, Republic of Korea; Department of Physiology, Biomedical Science Institute and Brain Korea 21 Project Center, Kyung Hee University School of Medicine, Seoul, Republic of Korea (J.S.K.); and Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, CA (C.S.C.).
authors.forename: Young-Beom
authors.initials: YB
authors.lastname: Kim
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Woong Bin
authors.initials: WB
authors.lastname: Kim
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Shen
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Chung
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Han
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Colwell
authors.forename: Yang In
authors.initials: YI
authors.lastname: Kim
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood*; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage; D006973:Hypertension / Q000097:blood* / Q000139:chemically induced*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D001127:Arginine Vasopressin; D012965:Sodium Chloride
keywords: NKCC1; arginine vasopressin; gamma-aminobutyric acid; hypertension; sodium; supraoptic nucleus